Saturday, August 2, 2025 8/2/2025

Antibody targeting of ADAM8 for treatment of triple-negative breast cancer

Award Number: R44CA200161
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/15/2016
PERIOD OF PERFORMANCE END DATE: 08/31/2022

Group Awards By:

View Award Description

Antibody targeting of ADAM8 for treatment of triple-negative breast cancer - Triple-negative breast cancers (TNBCs) account for ~25% of breast cancer deaths and lack targeted therapies. We identified the non-essential, cell surface protein ADAM8 as an important target on TNBC. ADAM8 is present in 34% of primary TNBCs, and 48% of all breast cancer patient-derived metastases, but absent in normal breast tissues. High ADAM8 mRNA levels correlate with poor patient outcome. The ADAM8 Metalloproteinase (MP) and Disintegrin (DI) domains drive tumor growth and metastasis through release of pro-angiogenic factors and activation of β1-integrin on cancer cells, respectively. A research-only anti-ADAM8 mouse monoclonal antibody (mAb) that inhibits the MP and DI domains decreased TNBC tumor growth and metastasis, validating ADAM8 as a therapeutic target. A PCT patent application (US14/37857) was filed May 13, 2014 by Drs. Sonenshein, Mineva and Romagnoli, and Tufts University, with claims to target the ADAM8 MP + DI domains (dual antagonist antibody) for treatment of breast and other ADAM8-driven cancers (e.g., gastric, lung, pancreatic). In October 2014, Adecto Pharmaceuticals, Inc. (AP) was founded by the 3 inventors to develop ADAM8 antibody-based therapies for aggressive cancers. Successful completion of the aims of our Phase I STTR has led to: i) generation of anti-human ADAM8 mouse mAbs (termed ADPs) that inhibit both the MP and DI domains, and ii) identification of two lead candidates (ADP2/ADP13) that decrease growth and dissemination of TNBC cell line-derived (CLD) tumors and improve mouse survival. We propose ADAM8 dual antagonist antibody therapy will become a new component of TNBC care. Through discussions with oncologists, we identified recurrent brain metastasis-free TNBC as our first indication and a combination of humanized ADP (hADP) + Standard-of-Care (SoC) chemotherapy (CT) as the treatment regimen. Preliminary results with ADP13 + Nab-Paclitaxel (N-PAC) demonstrate robust reduction in tumor regrowth compared to N- PAC alone in support of this approach. Immunohistochemistry of 30 normal human tissues detected ADAM8 primarily in gastrointestinal neuroendocrine cells (NECs) and occasionally in stomach and lung inflammatory immune cells. This limited expression pattern suggests targeting ADAM8 carries a low risk of side effects. Our 3 aims are to: (1) Identify the most effective SoC CT (e.g., N-PAC/Cisplatin) + ADP combination using CLD and patient-derived xenograft models; (2) Generate humanized (hADP2/hADP13) variants by CDR grafting, identify a functional lead for each in cell-based assays and confirm activity in humanized mice; (3) Perform early safety studies (determine effects of ADAM8 inhibition on primary PBMCs and NECs; confirm hADP lack of immunogenicity & tissue cross-reactivity). These studies will identify a lead hADP with early safety data and an entry path to the clinic. Guidance from GLP & GMP consultants will ensure AP is ready to transition to IND studies and allow us to attract investors/strategic partners and Phase 2b funding for continued development and commercialization of a novel treatment for TNBC patients, who currently lack targeted therapies.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2019	ADECTO PHARMACEUTICALS, INC.	549 WASHINGTON ST	BROOKLINE	MA	02446	NORFOLK	USA	Cancer Treatment Research	000	3	11/15/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2019	ADECTO PHARMACEUTICALS, INC.	549 WASHINGTON ST	BROOKLINE	MA	02446	NORFOLK	USA	Cancer Treatment Research	000	3	7/20/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $1,044,282 )
2019	2019	ADECTO PHARMACEUTICALS, INC.	549 WASHINGTON ST	BROOKLINE	MA	02446	NORFOLK	USA	Cancer Treatment Research	002	3	7/23/2019	NON-COMPETING CONTINUATION	$1,000,000
2019	2019	ADECTO PHARMACEUTICALS, INC.	549 WASHINGTON ST	BROOKLINE	MA	02446	NORFOLK	USA	Cancer Detection and Diagnosis Research	003	3	7/31/2019	SUPPLEMENT FOR EXPANSION	$2,084
2019	2018	ADECTO PHARMACEUTICALS, INC.	549 WASHINGTON ST	BROOKLINE	MA	02446	NORFOLK	USA	Cancer Treatment Research	001	2	5/7/2019	COMPETING CONTINUATION	$42,198
2019	2018	ADECTO PHARMACEUTICALS, INC.	549 WASHINGTON ST	BROOKLINE	MA	02446	NORFOLK	USA	Cancer Treatment Research	000	2	2/13/2019	COMPETING CONTINUATION	$0
														Subtotal = $1,044,282

Issue Date FY: 2018 ( Subtotal = $1,000,000 )
2018	2018	ADECTO PHARMACEUTICALS, INC.	549 WASHINGTON ST	BROOKLINE	MA	02446	NORFOLK	USA	Cancer Treatment Research	000	2	8/29/2018	COMPETING CONTINUATION	$1,000,000
														Subtotal = $1,000,000

Grand Total All Awards = $2,044,282

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Antibody targeting of ADAM8 for treatment of triple-negative breast cancer

Award Number: R44CA200161

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 04/15/2016

PERIOD OF PERFORMANCE END DATE: 08/31/2022

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer